ABSTRACT Among its medical complications, type 2 diabetes mellitus in older adults is associated with a two-fold increase in the risk of hip and other low-trauma bone fractures. Paradoxically, this increased risk occurs despite a higher average bone mineral density. This increased fracture risk is likely multifactorial, stemming from metabolic dysfunction that results in both increased falls risk and decreased bone strength. However, fracture risk stratification currently is limited largely to bone density testing and clinical risk tools that do not perform adequately for adults with diabetes. Because bone is both a metabolic and structural tissue, metabolomics and biomechanical analyses would be particularly useful for developing and assessing new measures of fracture risk. The objective of this application is to develop and evaluate radiographic and laboratory biomarkers of fracture risk among older adults with diabetes, utilizing biomechanical and translational measures. The proposed research has the following aims: 1) Determine the association between metabolomic profiles and incident clinical fracture among older adults with diabetes; 2) Compare geometric and biomechanical measures at the femoral neck and intertrochanteric region among older adults with diabetes, with and without hip fracture. This application builds upon the prior published work and clinical expertise of the Principle Investigator, Dr. Richard Lee, and provides him additional research skills to assist with his career development goal of understanding the interaction of chronic medical conditions on the bone health of older adults, focusing on diabetes. Dr. Lee is a dual-trained Geriatrician and Endocrinologist with expertise in metabolic bone disease. The primary training goals of this proposal include the following: 1) Develop laboratory and analytical skills in translational science that will be used in the development and evaluation of clinical biomarkers, including ?omics technologies; 2) Acquire principles and skills in biomechanical engineering and materials science to integrate with clinical and epidemiological analyses. By integrating biomechanical engineering and metabolomics approaches with epidemiologic research to identify new markers of fracture risk, this application addresses a significant source of morbidity and mortality among an increasing proportion of older adults.